Platelet membrane biomimetic nanoparticle-targeted delivery of TGF-ß1 siRNA attenuates renal inflammation and fibrosis.

The progression of renal fibrosis to end-stage renal disease (ESRD) is significantly influenced by transforming growth factor-beta (TGF-beta) signal pathway. This study aimed to develop nanoparticles (PMVs@PLGA complexes) with platelet membrane camouflage, which can transport interfering RNA to target and regulate the TGF-ß1 pathway in damaged renal tissues. The aim is to reduce the severity of acute kidney injury and to reduce fibrosis in chronic kidney disease. Hence, we formulated PMVs@TGF-ß1-siRNA NP complexes and employed them for both in vitro and in vivo therapy. From the experimental findings we know that the PMVs@siRNA NPs could effectively target the kidneys in unilateral ureteral obstruction (UUO) mice and ischemia/reperfusion injury (I/R) mice. In animal models of treatment, PMVs@siRNA NP complexes effectively decreased the expression of TGF-ß1 and mitigated inflammation and fibrosis in the kidneys by blocking the TGF-ß1/Smad3 pathway. Therefore, these PMVs@siRNA NP complexes can serve as a promising biological delivery system for treating kidney diseases.

Characterization of Bacillus amyloliquefaciens PM415 as a potential bio-preserving probiotic.

Animal feed is vulnerable to fungal infections, and the use of bio-preserving probiotics has received increasing attention. In contrast to Lactobacillus and Bifidobacteria spp., fewer Bacillus spp. have been recognized as antifungal probiotics. Therefore, our objective was to screen antifungal strains and provide more Bacillus candidates to bridge this gap. Here, we screened 56 bacterial strains for cyclic lipopeptide genes and conducted an antifungal assay with Aspergillus niger as a representative fungus. We found that a Bacillus strain Bacillus amyloliquefaciens PM415, isolated from pigeon manure, exhibited the highest fungal inhibition activity as demonstrated by the confrontation assay and morphological observation under scanning electron microscope (SEM). Preliminary safety assessment and probiotic characterization revealed its non-pathogenic feature and stress tolerance capability. Whole genome sequencing of Bacillus amyloliquefaciens PM415 revealed a genome size of 4.16 Mbp and 84 housekeeping genes thereof were used for phylogenetic analysis showing that it is most closely related to Bacillus amyloliquefaciens LFB112. The in silico analysis further supported its non-pathogenic feature at the genomic level and revealed potential biosynthetic gene clusters responsible for its antifungal property. RNA-seq analysis revealed genome-wide changes in transportation, amino acid metabolism, non-ribosomal peptides (NRPs) biosynthesis and glycan degradation during fungal antagonism. Our results suggest that Bacillus amyloliquefaciens PM415 is a safe and effective probiotic strain that can prevent fungal growth in animal feeds.

Insights into the biosynthesis of palladium nanoparticles for oxygen reduction reaction by genetically engineered bacteria of Shewanella oneidensis MR-1.

Owing to the increasing need for green synthesis and environmental protection, the utilization of biological organism-derived carbons as supports for noble-metal electrocatalysts has garnered public interest. Nevertheless, the mechanism by which microorganisms generate nanometals has not been fully understood yet. In the present study, we used genetically engineered bacteria of Shewanella oneidensis MR-1 (∆SO4317, ∆SO4320, ∆SO0618 and ∆SO3745) to explore the effect of surface substances including biofilm-associated protein (bpfA), protein secreted by type I secretion systems (TISS) and type II secretion systems (T2SS), and lipopolysaccharide in microbial synthesis of metal nanoparticles. Results showed Pd/∆SO4317 (the catalyst prepared with the mutant ∆SO4317) shows better performance than other biocatalysts and commercial Pd/C, where the mass activity (MA) and specific activity (SA) of Pd/∆SO4317 are 3.1 and 2.1 times higher than those of commercial Pd/C, reaching 257.49 A g-1 and 6.85 A m-2 respectively. It has been found that the exceptional performance is attributed to the smallest particle size and the presence of abundant functional groups. Additionally, the absence of biofilms has been identified as a crucial factor in the formation of high-quality bio-Pd. Because the absence of biofilm can minimize metal agglomeration, resulting in uniform particle size dispersion. These findings provide valuable mechanical insights into the generation of biogenic metal nanoparticles and show potential industrial and environmental applications, especially in accelerating oxygen reduction reactions.

Linear resistivity at van Hove singularities in twisted bilayer WSe2.

Different mechanisms driving a linear temperature dependence of the resistivity ρ ∼ T at van Hove singularities (VHSs) or metal-insulator transitions when doping a Mott insulator are being debated intensively with competing theoretical proposals. We experimentally investigate this using the exceptional tunability of twisted bilayer (TB) WSe2 by tracking the parameter regions where linear-in-T resistivity is found in dependency of displacement fields, filling, and magnetic fields. We find that even when the VHSs are tuned rather far away from the half-filling point and the Mott insulating transition is absent, the T-linear resistivity persists at the VHSs. When doping away from the VHSs, the T-linear behavior quickly transitions into a Fermi liquid behavior with a T2 relation. No apparent dependency of the linear-in-T resistivity, besides a rather strong change of prefactor, is found when applying displacement fields as long as the filling is tuned to the VHSs, including D ∼ 0.28 V/nm where a high-order VHS is expected. Intriguingly, such non-Fermi liquid linear-in-T resistivity persists even when magnetic fields break the spin-degeneracy of the VHSs at which point two linear in T regions emerge, for each of the split VHSs separately. This points to a mechanism of enhanced scattering at generic VHSs rather than only at high-order VHSs or by a quantum critical point during a Mott transition. Our findings provide insights into the many-body consequences arising out of VHSs, especially the non-Fermi liquid behavior found in moiré materials.

The Pd (II) Reduction Mechanisms in Bacillus megaterium Y-4 Revealed by Proteomic Analysis.

Many studies have been conducted on the microbial reduction of Pd (II) to palladium nanoparticles (Pd-NPs) due to the environmental friendliness, low cost, and the decreased toxicity of Pd (II) ions. In this study, we investigate the reduction mechanism of Pd (II) by Bacillus megaterium Y-4 through proteomics. The data are available via ProteomeXchange with identifier PXD049711. Our results revealed that B. megaterium Y-4 may use the endogenous electron donor (NAD(P)H) generated by nirB, tdh, and fabG and reductase to reduce Pd (II) to Pd-NPs. The expression levels of fabG, tdh, gudB, and rocG that generate NAD(P)H were further increased, and the number of reduced Pd-NPs was further increased with the exogenous electron donor sodium formate. Endogenous electron mediators such as quinones and flavins in B. megaterium Y-4 can further enhance Pd (II) reduction. The findings provided invaluable information regarding the reduction mechanism of Pd (II) by B. megaterium Y-4 at the proteome level.

Research on the factors influencing the process of prefabricated fragments penetrating finite thickness concrete.

The damage to the back of the target plate is a phenomenon that occurs when concrete is subjected to high-speed impact. In order to study the motion parameters of prefabricated spherical fragments penetrating finite thickness concrete targets at high speeds and the occurrence rules of concrete damage, as well as the impact of target back damage on the motion of fragments, experiments were conducted on 100 mm finite thickness concrete targets with prefabricated spherical fragments. The concrete model parameters in LS-DYNA were modified based on the residual velocity of fragments, and numerical simulations were conducted on the penetration of prefabricated fragments with different impact velocities and concrete target plates with different thicknesses. By analyzing the location of concrete target plate damage, the relationship between concrete thickness and concrete damage was obtained; Combining the motion parameters of fragment penetration process, the phenomenon of concrete collapse was linked to fragment motion, and the influence of concrete thickness on fragment motion parameters was analyzed. The results indicate that the thickness of the finite thickness concrete target plate and the penetration speed of fragments have a significant impact on the damage state of the target back, and further affect the motion change response stage during the penetration process of prefabricated fragments.

A karst-inspired hierarchical Mg/Al layered double hydroxide with a high entropy-driven process for interception and storage.

Karstification plays a crucial role in forming magnificent scenery, and storing oil, natural gas, mineral resources, and water. Through the inspiration of karstification, a hierarchical layered double hydroxide (LDH) with funnel-like and cave-like structures (called Karst-LDH) is formed by the dissolution of acrylic acid/water solution. Meanwhile, the results of transmission electron microscopy (TEM) and scanning electron microscopy (SEM) show that Karst-LDH has complicated and interconnected internal pipe networks. The actual maximum phosphate adsorption capacity of Karst-LDH reaches 126.38 mg g-1 due to the unique structures, protonation, ligand exchange, ion exchange, and hydrogen bonding, which is over ten times that of general LDH with a regular hexagonal structure. The results of isotherms and thermodynamics also indicate that Karst-LDH conforms to more heterogeneous and multilayer adsorption with a higher entropy-driven process. Karst-LDH exhibits good selectivity for chloride and nitrate ions. The change in the frontier orbital interaction between phosphate and different LDHs is a significant reason for quick macropore transmission, mesopore interception, and finally, phosphate storage in Karst-LDH. This work provides an efficient way for the design and fabrication of high adsorption performance materials with unique karst-type structures, which can be used for multiple fields potentially.

Middle mediastinal paraganglioma: A case report and review of the literature.

RATIONAL: Paragangliomas are rare and can occur in many places throughout the body, but mediastinal paragangliomas are even rarer, accounting for less than 0.3% of mediastinal masses. Extremely susceptible to misdiagnosis and mistreatment, which may lead to the death of the patient. PATIENT CONCERNS: We report a case of a giant paraganglioma of the middle mediastinum. A 40-year-old woman was admitted to the hospital with a rib fracture and a chest computed tomography suggesting a giant occupying tumor in the middle mediastinum. DIAGNOSIS: Immunohistochemistry revealed positive for S100 fraction and Syn, focally positive for CgA, while negative for CKp and succinate dehydrogenase complex iron sulfur subunit B gene, and Ki67index ≈ 5%. The imaging and immunohistochemical features suggested a final diagnosis of Paragangliomas. INTERVENTIONS: This patient underwent lateral open heart surgery to remove a mediastinal mass. OUTCOMES: One month after being discharged, the patient was contacted by phone for a follow-up visit and reported feeling OK. Unfortunately, as of the date of submission, the patient did not come to our hospital for review. LESSONS: Mediastinal paraganglioma as a rare and potentially malignant tumor susceptible to misdiagnosis and mistreatment. Organ pathology examination is the gold standard for diagnosis, and surgery is an important treatment method. A clear diagnosis and thorough preoperative examination are important guarantees for the success of surgery.

Efficient removal of purine compounds from solutions via biomass carbons derived from pomelo peel.

The high purine diet could result in the increase of the level of blood uric acid, causing serious health problems such as hyperuricemia, gout, nephropathy and cardiovascular diseases. To find out a safe, cheap and super adsorption material for removing purines in stomach or pretreating high-purine beverages, we used different tissues of pomelo peel to prepare biomass carbon by drying, chemical modification and carbonization and then applied it to remove purine compounds in strong acidic solution, beer and soybean milk. The characteristic analysis of pomelo-peel-derived carbons (PPCs) indicated that the preparation methods significantly affected the structures and adsorption capacities of PPCs. Compared with the biomass carbon derived from bamboo, PPCs exhibited higher adsorption capabilities for purine compounds in strong acidic solution (adsorption rates > 99% in 15 min) and soybean milk (adsorption rates > 56% in 30 min) but slightly lower adsorption capabilities in beer (adsorption rates > 52% in 30 min). In addition, the adsorption capabilities of PPCs for purine compounds in beer and soybean milk were not obviously affected by temperatures. Therefore, PPCs are promising absorbents for applications in removing purine compounds from beverages to produce low-purine, healthier products for treating hyperuricemia. The strong adsorption capabilities of PPCs on purine compounds in strong acidic environment also provides a possibility of using the PPCs as food additives for removing purines in stomach for healthcare applications such as gout prevention after confirming their biosafety.

Backbone 1H, 15N and 13C resonance assignments for dengue NS2B without the NS3 protease cofactor region in detergent micelles.

Dengue virus is an important human pathogen affecting people especially in tropical and subtropical regions. Its genome encodes seven non-structural proteins that are important for viral assembly and replication. Dengue NS2B is a membrane protein containing four transmembrane helices and involved in protein-protein interactions. Its transmembrane helices are critical for location of NS2B on the cell membrane while one cytoplasmic region composed of approximately 40 amino acids serves as a cofactor of viral NS3 protease by forming a tight complex with the N-terminal region of NS3. Here, we report the backbone resonance assignments for a dengue NS2B construct referred to as mini-NS2B containing only the transmembrane regions without NS3 cofactor region in detergent micelles. Mini-NS2B exhibits well-dispersed cross-peaks in the 1H-15N-HSQC spectrum and contains four helices in solution. The available mini-NS2B and its assignment will be useful for determining the structure of NS2B and identifying small molecules binding to the transmembrane regions.

Targeting RNA-binding proteins with small molecules: Perspectives, pitfalls and bifunctional molecules.

RNA-binding proteins (RBPs) play vital roles in organisms through binding with RNAs to regulate their functions. Small molecules affecting the function of RBPs have been developed, providing new avenues for drug discovery. Herein, we describe the perspectives on developing small molecule regulators of RBPs. The following types of small molecule modulators are of great interest in drug discovery: small molecules binding to RBPs to affect interactions with RNA molecules, bifunctional molecules binding to RNA or RBP to influence their interactions, and other types of molecules that affect the stability of RNA or RBPs. Moreover, we emphasize that the bifunctional molecules may play important roles in small molecule development to overcome the challenges encountered in the process of drug discovery.

Vertical sleeve gastrectomy-derived gut metabolite licoricidin activates beige fat thermogenesis to combat obesity.

Obesity is a chronic metabolic disease, affecting individuals throughout the world. Bariatric surgery such as vertical sleeve gastrectomy (VSG) provides sustained weight loss and improves glucose homeostasis in obese mice and humans. However, the precise underlying mechanisms remain elusive. In this study, we investigated the potential roles and the mechanisms of action of gut metabolites in VSG-induced anti-obesity effect and metabolic improvement. Methods: High-fat diet (HFD)-fed C57BL/6J mice were subjected to VSG. Energy dissipation in mice was monitored using metabolic cage experiments. The effects of VSG on gut microbiota and metabolites were determined by 16S rRNA sequencing and metabolomics, respectively. The metabolic beneficial effects of the identified gut metabolites were examined in mice by both oral administration and fat pad injection of the metabolites. Results: VSG in mice greatly increased thermogenic gene expression in beige fat, which was correlated with increased energy expenditure. VSG reshaped gut microbiota composition, resulting in elevated levels of gut metabolites including licoricidin. Licoricidin treatment promoted thermogenic gene expression in beige fat by activating the Adrb3-cAMP-PKA signaling pathway, leading to reduced body weight gain in HFD-fed mice. Conclusions: We identify licoricidin, which mediates the crosstalk between gut and adipose tissue in mice, as a VSG-provoked anti-obesity metabolite. Identification of anti-obesity small molecules should provide new insights into treatment options for obesity and its associated metabolic diseases.

Effect and formulation of ecolabel policy: A perspective of green supply chain decision and coordination.

Ecolabel policy has become an important strategy to encourage the consumption of green products throughout the world, contributing to sustainable development which is an inevitable choice for human society. Considering the manufacturer's reputation, consumer's environmental awareness, and effects of ecolabel certification on product demand, this study proposes several Stankelberg game models containing one manufacturer and one retailer to compare the optimal decisions and the impacts on the green supply chain with/without ecolabel certification, where four different scenarios are investigated in the centralized and decentralized situations. The results indicate that the ecolabel policy only functions below a threshold associated with the consumer's environmental awareness, which is higher in the decentralized situation. On the contrary, the optimal ecolabel standard in the centralized decision-making situation is higher than that in the decentralized ones if maximizing the environmental benefit. For the manufacturer, only when producing products as the ecolabel standard can it get the optimal profit. Finally, a wholesale price contract with the manufacturer's reputation is proposed, which improves the product's green degree and the environmental benefit to the optimal level in a decentralized supply chain.

Evidence That DDR1 Promotes Oligodendrocyte Differentiation during Development and Myelin Repair after Injury.

Oligodendrocytes generate myelin sheaths vital for the formation, health, and function of the central nervous system. Mounting evidence suggests that receptor tyrosine kinases (RTKs) are crucial for oligodendrocyte differentiation and myelination in the CNS. It was recently reported that discoidin domain receptor 1 (Ddr1), a collagen-activated RTK, is expressed in oligodendrocyte lineage. However, its specific expression stage and functional role in oligodendrocyte development in the CNS remain to be determined. In this study, we report that Ddr1 is selectively upregulated in newly differentiated oligodendrocytes in the early postnatal CNS and regulates oligodendrocyte differentiation and myelination. Ddr1 knock-out mice of both sexes displayed compromised axonal myelination and apparent motor dysfunction. Ddr1 deficiency alerted the ERK pathway, but not the AKT pathway in the CNS. In addition, Ddr1 function is important for myelin repair after lysolecithin-induced demyelination. Taken together, the current study described, for the first time, the role of Ddr1 in myelin development and repair in the CNS, providing a novel molecule target for the treatment of demyelinating diseases.

Dengue virus NS4B protein as a target for developing antivirals.

Dengue virus is an important pathogen affecting global population while no specific treatment is available against this virus. Effort has been made to develop inhibitors through targeting viral nonstructural proteins such as NS3 and NS5 with enzymatic activities. No potent inhibitors entering clinical studies have been developed so far due to many challenges. The genome of dengue virus encodes four membrane-bound nonstructural proteins which do not possess any enzymatic activities. Studies have shown that the membrane protein-NS4B is a validated target for drug discovery and several NS4B inhibitors exhibited antiviral activities in various assays and entered preclinical studies.. Here, we summarize the recent studies on dengue NS4B protein. The structure and membrane topology of dengue NS4B derived from biochemical and biophysical studies are described. Function of NS4B through protein-protein interactions and some available NS4B inhibitors are summarized. Accumulated studies demonstrated that cell-based assays play important roles in developing NS4B inhibitors. Although the atomic structure of NS4B is not obtained, target-based drug discovery approach become feasible to develop NS4B inhibitors as recombinant NS4B protein is available.

Perspectives on Converting Keratin-Containing Wastes Into Biofertilizers for Sustainable Agriculture.

Keratin-containing wastes become pollution to the environment if they are not treated properly. On the other hand, these wastes can be converted into value-added products applicable to many fields. Organic fertilizers and biofertilizers are important for sustainable agriculture by providing nutrients to enhance the growth speed of the plant and production. Keratin-containing wastes, therefore, will be an important resource to produce organic fertilizers. Many microorganisms exhibit capabilities to degrade keratins making them attractive to convert keratin-containing wastes into valuable products. In this review, the progress in microbial degradation of keratins is summarized. In addition, perspectives in converting keratin into bio- and organic fertilizers for agriculture are described. With proper treatment, feather wastes which are rich in keratin can be converted into high-value fertilizers to serve as nutrients for plants, reduce environmental pressure and improve the quality of the soil for sustainable agriculture.

Structures and Dynamics of Dengue Virus Nonstructural Membrane Proteins.

Dengue virus is an important human pathogen threating people, especially in tropical and sub-tropical regions. The viral genome has one open reading frame and encodes one polyprotein which can be processed into structural and nonstructural (NS) proteins. Four of the seven nonstructural proteins, NS2A, NS2B, NS4A and NS4B, are membrane proteins. Unlike NS3 or NS5, these proteins do not harbor any enzymatic activities, but they play important roles in viral replication through interactions with viral or host proteins to regulate important pathways and enzymatic activities. The location of these proteins on the cell membrane and the functional roles in viral replication make them important targets for antiviral development. Indeed, NS4B inhibitors exhibit antiviral activities in different assays. Structural studies of these proteins are hindered due to challenges in crystallization and the dynamic nature of these proteins. In this review, the function and membrane topologies of dengue nonstructural membrane proteins are presented. The roles of solution NMR spectroscopy in elucidating the structure and dynamics of these proteins are introduced. The success in the development of NS4B inhibitors proves that this class of proteins is an attractive target for antiviral development.

Secondary Structures of the Transmembrane Domain of SARS-CoV-2 Spike Protein in Detergent Micelles.

Spike protein of SARS-CoV-2 contains a single-span transmembrane (TM) domain and plays roles in receptor binding, viral attachment and viral entry to the host cells. The TM domain of spike protein is critical for viral infectivity. Herein, the TM domain of spike protein of SARS-CoV-2 was reconstituted in detergent micelles and subjected to structural analysis using solution NMR spectroscopy. The results demonstrate that the TM domain of the protein forms a helical structure in detergent micelles. An unstructured linker is identified between the TM helix and heptapeptide repeat 2 region. The linker is due to the proline residue at position 1213. Side chains of the three tryptophan residues preceding to and within the TM helix important for the function of S-protein might adopt multiple conformations which may be critical for their function. The side chain of W1212 was shown to be exposed to solvent and the side chains of residues W1214 and W1217 are buried in micelles. Relaxation study shows that the TM helix is rigid in solution while several residues have exchanges. The secondary structure and dynamics of the TM domain in this study provide insights into the function of the TM domain of spike protein.

1H, 13C and 15N resonance assignments of the first BIR domain of cellular inhibitor of apoptosis protein 1.

Cellular inhibitor of apoptosis protein-1 (cIAP-1) is member of inhibitor of apoptosis proteins (IAPs) which can affect apoptosis through interactions with caspases. cIAP-1 is a multi-domain protein and able to regulate apoptosis through interactions with proteins such as caspases and possesses E3 ligase activity. Human cIAP-1 contains three baculovirus IAP repeat (BIR) domains which are critical for protein-protein interactions. Here, we report NMR resonance assignments of the first BIR domain of human cIAP. Its secondary structures in solution were determined based on the assigned resonances. The dynamics of this domain was obtained, and our hydrogen-deuterium exchange experiment reveals that the first helix in BIR1 is exposed to the solvent. The availability of assignments of backbone and side chain resonances will be useful for probing protein-protein interactions.